The molecular mechanisms that define asymptomatic bacteriuria (ABU) Escherichia coli colonization of the human urinary tract
remain to be properly elucidated. Here, we utilize ABU E. coli strain 83972 as a model to dissect the contribution of siderophores
to iron acquisition, growth, fitness, and colonization of the urinary tract. We show that E. coli 83972 produces enterobactin, salmochelin,
aerobactin, and yersiniabactin and examine the role of these systems using mutants defective in siderophore biosynthesis
and uptake. Enterobactin and aerobactin contributed most to total siderophore activity and growth in defined irondeficient
medium. No siderophores were detected in an 83972 quadruple mutant deficient in all four siderophore biosynthesis
pathways; this mutant did not grow in defined iron-deficient medium but grew in iron-limited pooled human urine due to iron
uptake via the FecA ferric citrate receptor. In a mixed 1:1 growth assay with strain 83972, there was no fitness disadvantage of the
83972 quadruple biosynthetic mutant, demonstrating its capacity to act as a “cheater” and utilize siderophores produced by the
wild-type strain for iron uptake. An 83972 enterobactin/salmochelin double receptor mutant was outcompeted by 83972 in human
urine and the mouse urinary tract, indicating a role for catecholate receptors in urinary tract colonization.